Crystalline pharmaceutical and methods of preparation and use thereof
View Patent ↗Novel crystalline polymorphic forms, Forms A, B, C, D, and E of a compound of Formula I, which has been found to be a potent inhibitor of LFA-1, are disclosed. Methods of preparation and uses thereof in the treatment of LFA-1 mediated diseases are also disclosed in this invention.
1. A composition comprising an isolated compound of Formula I:
or a salt thereof, wherein said compound is synthesized according to a method comprising the steps:
a) performing base hydrolysis of Formula AA with a base in an aprotic solvent, or performing acid hydrolysis of Formula AA with an acid in an aprotic solvent:
wherein R is a carbon containing moiety; and
b) isolating a compound of Formula I or a salt thereof, with an enantiomeric excess of greater than about 90%;
wherein said composition has a lower level of residual palladium compared to a composition comprising a compound of Formula I or a salt thereof prepared by palladium-catalyzed transfer hydrogenolysis.
2. The composition of claim 1 , wherein the aprotic solvent is dioxane.
3. The composition of claim 1 , wherein the base is sodium hydroxide.
4. The composition of claim 1 , wherein the acid is hydrogen chloride.
5. The composition of claim 1 , wherein R is a substituted or unsubstituted group selected from lower alkyl, lower alkenyl, lower alkynyl, cyclo(lower)alkyl, cyclo(lower)alkenyl, aryl, aralkyl, heterocyclyl, and heteroaryl groups.
6. The composition of claim 1 , wherein the residual palladium in the composition is less than about 100 ppm.
7. The composition of claim 1 , wherein the residual palladium in the composition is less than about 50 ppm.
8. The composition of claim 1 , wherein the residual palladium in the composition is less than about 10 ppm.
9. The composition of claim 1 , wherein the residual palladium in the composition is less than about 1 ppm.